1) Pulmonary embolism (PE) was first described in the 18th century and risk factors include both modifiable factors like obesity and smoking as well as non-modifiable factors like age, family history, and cancer. 2) PE is classified by size from massive to small, with massive PE affecting half the pulmonary arteries and causing shock while small PE causes few symptoms. 3) Diagnosis involves assessment of clinical probability with tools like Wells Criteria followed by tests like CT, ventilation-perfusion scan, or ultrasound depending on the patient's situation. 4) Treatment involves anticoagulation with drugs like heparin or novel oral anticoagulants, with duration depending on prov

1. PULMONARY THROMBOEMBOLISM

2. History Susrutha describes swollen painful leg circa 600-1000 BCE Giovanni battistamargagni recognized blood clots in pulmonary vessels in patients suffering sudden death in 1761 In mid 1800 jean cruveilheir a french pathologist suggested role of venous inflammation& thrombosis

3. Virchow triad Intimal vessel injury Stasis hypercoagulability

4. The classic description of radiographic findings by westermark in 1938 The description of electrocardiographic corpulmonale by Mcginn and white 1935 Echo in the diagnosis of PE by has its origin in case report by Covarrubias & colleagues in 1977

5. -- Modifiable Risk Factors for Venous Thromboembolism Obesity Metabolic syndrome Cigarette smoking Hypertension Abnormal lipid profile High consumption of red meat and low consumption of fish, fruits, and vegetables

6. -- Major Risk Factors for Venous Thromboembolism That Are Not Readily Modifiable Advancing age Arterial disease, including carotid and coronary disease Personal or family history of venous thromboembolism Recent surgery, trauma, or immobility, including stroke Congestive heart failure Chronic obstructive pulmonary disease Acute infection Air pollution Long-haul air travel Pregnancy, oral contraceptive pills, or postmenopausal hormone replacement therapy Pacemaker, implantable cardiac defibrillator leads, or indwelling central venous catheter

7. Hypercoagulable states Factor V Leiden resulting in activated protein C resistance Prothrombin gene mutation 20210 Antithrombin deficiency Protein C deficiency Protein S deficiency Antiphospholipid antibody syndrome

9. Symptoms Otherwise unexplained dyspnea Chest pain, either pleuritic or “atypical” Anxiety CoughSigns Tachypnea Tachycardia Low-grade fever Left parasternal lift Tricuspid regurgitant murmur Accentuated P2 Hemoptysis Leg edema, erythema, tenderness

11. -- Simplified Wells Criteria to Assess Clinical Likelihood of Pulmonary Embolism >1 score point = high probability ≤1 score point = non–high probability SCORE POINTS DVT symptoms or signs 1 An alternative diagnosis is less likely than PE 1 Heart rate >100/min 1 Immobilization or surgery within 4 weeks 1 Prior DVT or PE 1 Hemoptysis 1 Cancer treated within 6 months or metastatic 1

13. Massive Pulmonary Embolism Patients with massive PE are susceptible to cardiogenic shock and multisystem organ failure. Renal insufficiency, hepatic dysfunction, and altered mentation are common findings. Thrombosis is widespread, affecting at least half of the pulmonary arterial vasculature. Clot is typically present bilaterally. Dyspnea is usually the most noticeable symptom; chest pain is unusual transient cyanosis is common, and systemic arterial hypotension requiring pressor support is frequent

14. Moderate to Large (Submassive) Pulmonary Embolism These patients frequently present with moderate or severe right ventricular hypokinesis as well as elevations in troponin, pro-BNP, or BNP, but they maintain normal systemic arterial pressure. Usually, one third or more of the pulmonary artery vasculature is obstructed. If there is no prior history of cardiopulmonary disease, they may appear clinically well, but this initial impression is often misleading. They are at risk for recurrent PE, even with adequate anticoagulation.

15. Most survive, but they may require escalation of therapy with pressor support or mechanical ventilation. Therefore, especially if moderate or severe right ventricular dysfunction persists, one should consider thrombolytic therapy or embolectomy. If neither thrombolysis nor embolectomy appears warranted, placement of an inferior vena caval filter is controversial but may be employed as a “back-up” in case heparin anticoagulation fails.

16. Small to Moderate Pulmonary Embolism This presentation is characterized by normal systemic arterial pressure, no cardiac biomarker release normal right ventricular function. Patients appear clinically stable. Adequate anticoagulation results in an excellent clinical outcome.

17. Pulmonary Infarction This syndrome is characterized by pleuritic chest pain that may be unremitting or may wax and wane. The pleurisy is occasionally accompanied by hemoptysis. The embolus usually lodges in the peripheral pulmonary arterial tree, near the pleura. Tissue infarction usually occurs 3 to 7 days after embolism. The syndrome often includes fever, leukocytosis, elevated erythrocyte sedimentation rate, and radiologic evidence of infarction.

18. Nonthrombotic Pulmonary Embolism They include fat, tumor, air, and amniotic fluid Fat embolism syndrome is most often observed after blunt trauma complicated by long bone fractures. Air embolus can occur during placement or removal of a central venous catheter. Amniotic fluid embolism may be catastrophic and is characterized by respiratory failure, cardiogenic shock, and disseminated intravascular coagulation. Intravenous drug abusers sometimes self-inject hair, talc, and cotton that contaminate the drug they have acquired. These patients also have susceptibility to septic PE, which can cause endocarditis of the tricuspid or pulmonic valves.

19. Differential Diagnosis of Pulmonary Embolism Anxiety, pleurisy, costochondritis Pneumonia, bronchitis Myocardial infarction Pericarditis Congestive heart failure Idiopathic pulmonary hypertension

20. Biomarkers for detecting myocardial injury BNP & NT- Pro BNP cTroponin T & I H-FABP (Heart type) Growth differentiation factor -15

21. Plasma D-Dimer Assay This blood screening test relies on the principle that most patients with PE have ongoing endogenous fibrinolysis that is not effective enough to prevent PE but that does break down some of the fibrin clot to d-dimers Although elevated plasma concentrations of d-dimers are sensitive for the presence of PE, they are not specific. Levels are elevated for at least 1 week postoperatively and are increased in patients with myocardial infarction, sepsis, cancer, or almost any other systemic illness. Therefore, the plasma d-dimer assay is ideally suited for outpatients or emergency department patients who have suspected PE but no coexisting acute systemic illness. This test is generally not useful for acutely ill hospitalized inpatients because their d-dimer levels are usually elevated. A normal d-dimer assay appears to be as diagnostically useful as a normal lung scan to exclude PE. patients with a low clinical probability of PE who had negative d-dimer results, additional diagnostic testing was not necessary.

22. Electrocardiographic Signs of Pulmonary Embolism Sinus tachycardia Incomplete or complete right bundle branch block Right-axis deviation T wave inversions in leads III and aVF or in leads V1-V4 S wave in lead I and a Q wave and T wave inversion in lead III (S1Q3T3) QRS axis greater than 90 degrees or an indeterminate axis Atrial fibrillation or atrial flutter

23. Chest Radiography A near-normal radiograph in the setting of severe respiratory compromise is highly suggestive of massive PE. Major chest radiographic abnormalities are uncommon. Focal oligemia (Westermark sign) indicates massive central embolic occlusion. A peripheral wedge-shaped density above the diaphragm (Hampton hump) usually indicates pulmonary infarction. Subtle abnormalities suggestive of PE include enlargement of the descending right pulmonary artery. The vessel often tapers rapidly after the enlarged portion. PE.

25. Echocardiographic Signs of Pulmonary Embolism Right ventricular enlargement or hypokinesis, especially free wall hypokinesis, with sparing of the apex (the McConnell sign) Interventricularseptal flattening and paradoxical motion toward the left ventricle, resulting in a D-shaped left ventricle in cross section Tricuspid regurgitation Pulmonary hypertension with a tricuspid regurgitant jet velocity >2.6 m/sec Loss of respiratory-phasic collapse of the inferior vena cava with inspiration Dilated inferior vena cava without physiologic inspiratory collapse Direct visualization of thrombus (more likely with transesophageal echocardiography)

26. Chest Computed Tomography Size, location, and extent of thrombus Other diagnoses that may coexist with PE or explain PE symptoms: Pneumonia Atelectasis Pericardial effusion Pneumothorax Left ventricular enlargement Pulmonary artery enlargement, suggestive of pulmonary hypertension Age of thrombus: acute, subacute, chronic Location of thrombus: pulmonary arteries, pelvic veins, deep leg veins, upper extremity veins Right ventricular enlargement Contour of the interventricular septum: whether it bulges toward the left ventricle, thus indicating right ventricular pressure overload Incidental masses or nodules in lung

29. Magnetic Resonance Imaging Gadolinium-enhanced magnetic resonance angiography (MRA) is far less sensitive than CT for the detection of PE. However, unlike chest CT or catheter-based pulmonary angiography, MRA does not require ionizing radiation or injection of iodinated contrast agent. In addition, magnetic resonance pulmonary angiography can assess right ventricular size and function. Three-dimensional MRA can be carried out during a single breath-hold and may provide high resolution from the main pulmonary artery through the segmental pulmonary artery branches.

30. Pulmonary Angiography Invasive pulmonary angiography was formerly the reference standard for diagnosis of PE, but it is now rarely performed. It is an uncomfortable and potentially risky procedure. However, pulmonary angiography is required when interventions are planned, such as suction catheter embolectomy, mechanical clot fragmentation, or catheter-directed thrombolysis. In cases of chronic thromboembolic PE, pulmonary arteries appear pouched. The thrombus usually organizes with a concave edge. Bandlike defects called webs may be present, in addition to intimal irregularities and abrupt narrowing or occlusion of lobar vessels.

31. Lung scans depend on expert interpretation, and there is a great deal of interobserver variability even among experts. Only three indications to obtain a lung scan exist: (1) renal insufficiency, (2) anaphylaxis to intravenous contrast agent that cannot be suppressed with high-dose corticosteroids (3) pregnancy (lower radiation exposure to the fetus).

32. Contrast Venography Although contrast phlebography was once the reference standard for DVT diagnosis, venograms are now rarely obtained . Venography is costly, invasive, and potentially harmful. It can cause contrast-induced renal failure, anaphylaxis, or chemical phlebitis. Furthermore, difficulty in interpretation of contrast venograms causes considerable disagreement among experienced readers. Invasive contrast phlebography is required, of course, for interventional procedures such as catheter-directed thrombolysis, suction embolectomy, angioplasty, stenting, and placement of an inferior vena caval filter. In patients undergoing total hip or knee replacement, contrast venography is more sensitive than venous ultrasonography for the diagnosis of acute DVT.

34. The Pulmonary Embolism Severity Index PREDICTOR SCORE POINTS Age, per year Age, in years Male sex 10 History of cancer 30 History of heart failure 10 History of chronic lung disease 10 Pulse ≥110/min 20 Systolic blood pressure <100 mm Hg 30 Respiratory rate ≥30/min 20 Temperature <36?C 20 Altered mental status 60 Arterial oxygen saturation <90% 20 Low prognostic risk is defined as ≤85 points.

35. Predictors of Increased Mortality Hemodynamic instability Right ventricular hypokinesis on echocardiogram Right ventricular enlargement on echocardiogram or chest CT scan Right ventricular strain on electrocardiogram Elevated cardiac biomarkers

42. Use of Heparin Before and After Thrombolysis 1 Discontinue the continuous infusion of intravenous UFH as soon as the decision has been made to administer thrombolysis. 2 Proceed to order thrombolysis. Use the U.S. Food and Drug Administration–approved regimen of alteplase 100 mg as a continuous infusion during 2 hours. 3 Do not delay the thrombolysis infusion by obtaining an activated partial thromboplastin time (aPTT) . 4 Infuse thrombolysis as soon as it becomes available. 5 At the conclusion of the 2-hour infusion, obtain a stat aPTT . 6 If the aPTT is 80 seconds or less (which is almost always the case), resume UFH as a continuous infusion without a bolus. 7 If the aPTT exceeds 80 seconds, hold off from resuming heparin for 4 hours and repeat the aPTT. At this time, the aPTT has virtually always declined to <80 seconds. If this is the case, resume continuous infusion of intravenous UFH without a bolus.

48. Synthetic pentasaccharides Synthetic direct thrombin inhibitors Fondaparinux idraprinux Dabigatran 220 mg or 150 mg/d

49. Fondaparinux Dosing for Patients with Acute Pulmonary Embolism or DVT weight <50 kg 50-100 kg >100 k dose 5 mg 7.5 mg 10 mg

50. Synthetic direct Factor Xa inhibitor Rivaroxaban 10mg/d oral Apixaban 2.5 mg bd Betrixaban 15mg bd or 40 mg bd

51. Optimal Duration of Anticoagulation First provoked PE/proximal leg DVT 3 to 6 months First provoked upper extremity DVT or isolated calf DVT 3 months Second provoked VTE Uncertain Third VTE Indefinite duration Cancer and VTE Consider indefinite duration or until cancer is resolved Unprovoked PE/proximal leg DVT Consider indefinite duration First unprovoked calf DVT 3 months Second unprovoked calf DVT Uncertain

55. IVC FILTERS

61. Catheter Embolectomy Interventional catheterization techniques[for massive PE include mechanical fragmentation of thrombus with a standard pulmonary artery catheter, clot pulverization with a rotating basket catheter, percutaneousrheolyticthrombectomy and pigtail rotational catheter embolectomy. Another approach is mechanical clot fragmentation and aspiration, which can be combined if necessary with pharmacologic thrombolysis Pulmonary artery balloon dilation and stenting can also be considered. Successful catheter embolectomy rapidly restores normal blood pressure and decreases hypoxemia. Catheter techniques have been limited by poor maneuverability, mechanical hemolysis, macroembolization, and microembolization.

64. Surgical Embolectomy Emergency surgical embolectomy with cardiopulmonary bypass has reemerged as an effective strategy for management of patients with massive PE and systemic arterial hypotension or submassive PE with right ventricular dysfunction in whom contraindications preclude thrombolysis This operation is also suited for acute PE patients who require surgical excision of a right atrial thrombus or closure of a patent foramen ovale. Surgical embolectomy can also rescue patients refractory to thrombolysis.

65. Pregnancy & VTE

75. Before surgery

78. General surgery Unfractionated heparin 5000 units SC bid or tidor Enoxaparin 40 mg SC qdor Dalteparin 2500 or 5000 units SC qd

79. Major orthopedic surgery Warfarin (target INR 2 to 3) or Enoxaparin 30 mg SC bid or Enoxaparin 40 mg SC qdor Dalteparin 2500 or 5000 units SC qdor Fondaparinux 2.5 mg SC qd Rivaroxaban 10 mg qd (in Canada and Europe) Dabigatran 220 mg bid (in Canada and Europe

80. Neurosurgery Unfractionated heparin 5000 units SC bid or Enoxaparin 40 mg SC qdand Graduated compression stockings or intermittent pneumatic compression Consider surveillance lower extremity ultrasonography

81. Oncologic surgery Enoxaparin 40 mg SC qd Thoracic surgery Unfractionated heparin 5000 units SC tidand Graduated compression stockings or intermittent pneumatic compression

82. RISK IN HOSPITALIZED PATIENTS

87. Hospitalization with medical illness Unfractionated heparin 5000 units SC bid or tidor Enoxaparin 40 mg SC qdor Dalteparin 5000 units SC qdor Fondaparinux 2.5 mg SC qd (in patients with a heparin allergy such as heparin-induced thrombocytopenia) or Graduated compression stockings or intermittent pneumatic compression for patients with contraindications to anticoagulationConsider combination pharmacologic and mechanical prophylaxis for high-risk patients Consider surveillance lower extremity ultrasonography for intensive care unit patients

89. Women with HRT

92. Fat Embolism

97. THANK YOU

98. Massive Pulmonary Embolism Begin bolus high-dose intravenous unfractionated heparin as soon as massive pulmonary embolism is suspected. ▪ Begin continuous infusion of unfractionated heparin to achieve a target aPTT of at least 80 seconds. ▪ Try volume resuscitation with no more than 500 to 1000 mL of fluid. ▪ Excessive volume resuscitation will worsen right ventricular failure. ▪ Have a low threshold for administration of vasopressors and inotropes. ▪ Decide whether thrombolysis can be safely administered, without a high risk of major hemorrhage. ▪ If thrombolysis is too risky, consider placement of an inferior vena caval filter, catheter embolectomy, or surgical embolectomy. ▪ Do not use a combination of thrombolysis and vena caval filter insertion. The prongs of the filter insert into the caval wall. Concomitant thrombolysis predisposes to caval wall hemorrhage. ▪ Consider immediate referral to a tertiary care hospital specializing in massive pulmonary embolism.

101. increased pulmonary vascular resistance caused by vascular obstruction, neurohumoral agents, or pulmonary artery baroreceptors impaired gas exchange caused by increased alveolar dead space from vascular obstruction and hypoxemia from alveolar hypoventilation, low ventilation-perfusion units, and right-to-left shunting as well as impaired carbon monoxide transfer caused by loss of gas exchange surface; alveolar hyperventilation caused by reflex stimulation of irritant receptors; increased airway resistance due to bronchoconstriction; and decreased pulmonary compliance due to lung edema, lung hemorrhage, and loss of surfactant.